The purpose of this research proposal is to conduct basic and clinical studies of the biosynthesis and secretion, biochemistry and immunochemistry, and biological interactions of calcitonin and the other calcitropic hormones - parathyroid hormone and Vitamin D. The studies will be conducted both in vitro and in vivo. The in vitro studies will be conducted in monolayer cultures of hormone-producing cells. These studies in molecular biology will be designed to investigate the fundamental mechanisms which regulate the biosynthesis and secretion of the hormones. The in vivo studies will be conducted in humans and experimental animals. The rat will serve as the primary experimental model, although other pertinent animal models will also be used. In animals, systematic studies will be conducted in normal and abnormal physiological states. The studies will be designed to clarify the dynamic interrelationships that exist among the calcitropic hormones and that exist between the calcitropic hormones and other related bioactive substances such as gastrointestinal hormone, prostaglandins, and cyclic nucleotides. These experimental studies will provide a framework for studies in humans. The studies in humans will be also designed to further investigate the interactions among the calcitropic hormones and between the calcitropic hormones and other biological systems. These clinical studies will attempt to further establish the physiological significance of calcitonin in humans and its functional relationship to parathyroid hormone and Vitamin D. In addition, the primary or secondary role of calcitonin and the other calcitropic hormones in the pathogenesis of a variety of disease states, both skeletal and non-skeletal, will be further defined. All of the studies will be performed by the application of existing and planned competitive-protein-binding assays, including radioimmunoassays and radiometric assays, for each of the hormones and related factors. Assay measurements will be made in the basal state during provocative and suppressive tests of biosynthesis and secretion.